They release natural killer cells against cancer

Using various human immune cells known as killer cells Naturally, US researchers have revolutionized immunotherapy against several types of cancer. The key is neutralizing the protein that cancerous tumors use to stop natural killer (killer cellsin Spanish).

According to Xinxin Zhang, a professor of several biomedical disciplines at Albert Einstein College of Medicine and Montefiore Cancer Center and coordinator of a pilot study that appears in Journal of Clinical Research“We believe that the new immunotherapy we have developed has great potential to move into clinical trials in a variety of cancer types.”

With the introduction of monoclonal antibodies (known in scientific jargon as magic bullets), more than ten years ago a huge step forward was taken in the fight against cancer.

Taking as an example pembrolizumab And nivolumabDue to its mechanism of action, which involves releasing T cells from the immune system to attack tumor cells, scientists have been able to fight cancer with some effectiveness, but over time it has been proven that only 10 to 30% of patients treated magic bullets experience long-term improvement.

Now Albert Einstein’s research team has developed and applied an innovative strategy to improve efficiency checkpoint immune.

So, instead of harvesting T cells to fight cancer, Professor Zang’s team used various human immune cells (killer cells natural), with results this researcher calls “impressive.”

Checkpoint proteins

It is well known that the surface of immune cells is filled with receptors known as checkpointwhich prevent them from moving beyond their normal targets (pathogen-infected cells and cancer cells).

When recipients checkpoints Immune cells bind to proteins expressed by the body’s own normal cells, this interaction stops a possible attack by the immune cells. In maneuver reasonableMost types of cancer cells express proteins that bind to proteins checkpoint, fraud to immune cells so that they stop and do not attack the tumor.

Inhibitors checkpoint Immune antibodies are monoclonal antibodies designed to short-circuit interactions between immune cells and cancer cells by blocking tumor proteins or immune cell receptors that bind to tumor proteins. No brakes to prevent them, Immune cells can attack and destroy cancer cells.

Limited effectiveness of inhibitors checkpoints prompted Professor Zang to analyze ways checkpoints involving NK cells, which, like T cells, play an important role in eliminating unwanted cells.

These scientists studied the PVR protein, which is present in cancer cells. “We realized that PVR may be a very important protein that human cancers use to prevent the immune system from attacking.”, this researcher emphasizes.

Killer cell activity

PVR protein is usually absent or very scarce in normal tissues, but It is found in abundance in many types of tumors.including colorectal, ovarian, lung, esophagus, head and neck, stomach and pancreas, as well as myeloid leukemia and melanoma.

In addition, PVRs appear to inhibit T cell and NK cell activity by binding to a protein. checkpoint called TIGIT, which prompted attempts to disrupt the TIGIT/PVR pathway using monoclonal antibodies generated against it.

At the moment, More than a hundred clinical studies have been conducted targeting TIGIT., World. But recently, several studies, including two large phase 3 clinical trials, have failed to improve cancer outcomes.

Meanwhile, these scientists discovered that the PVR protein of cancer cells has another communication partner V killer cellswhich they call KIR2DL5.

At this point, Professor Zang believes that PVR suppresses NK cell activity not by binding to TIGIT, but by binding to KIR2DL5.. To confirm this hypothesis, his team synthesized a monoclonal antibody targeting KIR2DL5 and performed experiments. in vitro And in natural conditions.

In conclusion, they showed that KIR2DL5 – receptor checkpoint distributed on the surface of human NK cellswhich cancer PVR proteins use to suppress immune attack.

Killer cell attack

In a series of experiments in humanized animal models of various cancer types, these researchers demonstrated that their anti-KIR2DL5 monoclonal antibody, by blocking the KIR2DL5/PVR pathway, allowed killer cells They will attack with force and shrink human tumors.prolonging the survival of animals.

“These preclinical results give us hope that targeting the KIR2DL5/PVR pathway was a good idea and that The monoclonal antibody we developed can be an effective immunotherapy“, notes Professor Zang.

Dr. Zhang has previously developed and patented more than 10 immune checkpoint inhibitors. One of them is currently undergoing phase 2 clinical trials in China involving several hundred patients with advanced solid cancer (non-small cell lung cancer, small cell lung cancer, nasopharyngeal cancer, head and neck cancer, melanoma and lymphoma).

“Magic bullets” made in the laboratory

Monoclonal antibodies are laboratory-made molecules designed to act as surrogate antibodies that can repair, enhance, modify, or mimic the immune system’s attack on unwanted cells, such as cancer cells.

As Mayo Clinic experts explain, monoclonal antibodies work in different ways:

• Detect cancer cells

  Some cells of the immune system depend on antibodies to locate the target of attack. Cancer cells coated with monoclonal antibodies are easier to detect and destroy.

• Causes destruction of cell membranes

  Certain monoclonal antibodies can trigger an immune system response that can destroy the outer wall (membrane) of the cancer cell.

• Block cell growth

  Certain monoclonal antibodies block communication between a cancer cell and proteins that promote cell growth, an activity essential for cancer growth and survival.

• Prevent the growth of blood vessels

  For a cancer tumor to grow and survive, it needs a blood supply. Some monoclonal antibody drugs block interactions between proteins and cells necessary for the formation of new blood vessels.

• Block immune system inhibitors

  The body creates proteins that control the activity of immune system cells, preventing them from becoming overactive. Monoclonal antibodies can interfere with this process, allowing immune system cells to perform their function without restriction against cancer cells.

• Directly attacks cancer cells

  Some monoclonal antibodies can attack the cell more directly. When some of these antibodies bind to a cell, a series of events that occur inside the cell can cause it to self-destruct.

• Carry out radiation treatment

  Due to the ability of monoclonal antibodies to bind to a cancer cell, the antibody can be used as a tool for other treatments. When a monoclonal antibody binds to a small radioactive particle, it delivers radiation therapy directly to cancer cells and can minimize the effects of radiation on healthy cells.

• Carry out chemotherapy

  Likewise, some monoclonal antibodies bind to a chemotherapy drug, delivering the treatment directly to cancer cells and excluding healthy cells.

• Binds to cancer and immune cells

  Some drugs combine two monoclonal antibodies: one that binds to the cancer cell and the other to a specific immune system cell. This connection may stimulate the immune system to attack cancer cells.